Lustig M J, Cadet J, Boorstein R J, Teebor G W
Department of Pathology, New York University Medical Center, NY 10016.
Nucleic Acids Res. 1992 Sep 25;20(18):4839-45. doi: 10.1093/nar/20.18.4839.
5,6-dihydroxy-5,6-dihydrothymidine (thymidine glycol) is a major product of the reaction of thymidine with reactive oxygen species, including those generated by ionizing radiation. Thymidine glycol exists as 2 diastereomeric pairs by virtue of the chirality of the C(5) and C(6) atoms. A simple procedure is described for synthesizing and purifying each of the diastereomeric pairs separately. After brominating thymidine, the two trans 5-bromo-6-hydroxy-5,6-dihydrothymidine (thymidine bromohydrin) C(5) diastereomers were easily separated by High Performance Liquid Chromatography. Each thymidine bromohydrin was quantitatively converted to the corresponding diastereomeric thymidine glycol pair by reflux in aqueous solution. The concentrations at equilibrium of the cis (5S,6R),(5R,6S) and trans (5S,6S),(5R,6R) forms of the thymidine glycol diastereomers were determined and were 80% cis and 20% trans for the 5S pair and 87% cis and 13% trans for the 5R pair. At equilibrium, the rate of cis-trans epimerization of the two sets of diastereomers was essentially identical. The 5S diastereomeric pair was significantly more alkali labile than the 5R pair due to the higher concentration of the 5S trans epimer at equilibrium. This differential alkali lability was also manifest when the thymine glycol moiety was present in chemically oxidized poly(dA-dT).poly(dA-dT) indicating that the chemical differences between the diastereomeric pairs are preserved in DNA. These chemical differences may affect the biological properties of this important oxidative derivative of thymine in DNA.
5,6 - 二羟基 - 5,6 - 二氢胸苷（胸苷二醇）是胸苷与活性氧反应的主要产物，活性氧包括由电离辐射产生的那些。由于C(5)和C(6)原子的手性，胸苷二醇以2个非对映体对的形式存在。本文描述了一种分别合成和纯化各非对映体对的简单方法。在对胸苷进行溴化后，通过高效液相色谱法很容易分离出两种反式5 - 溴 - 6 - 羟基 - 5,6 - 二氢胸苷（胸苷溴醇）C(5)非对映体。通过在水溶液中回流，每个胸苷溴醇都定量地转化为相应的非对映体胸苷二醇对。测定了胸苷二醇非对映体的顺式（5S,6R）、（5R,6S）和反式（5S,6S）、（5R,6R）形式在平衡时的浓度，5S对为80%顺式和20%反式，5R对为87%顺式和13%反式。在平衡时，两组非对映体的顺 - 反差向异构化速率基本相同。由于平衡时5S反式差向异构体的浓度较高，5S非对映体对比5R对明显更易被碱降解。当胸腺嘧啶二醇部分存在于化学氧化的聚（dA - dT）·聚（dA - dT）中时，这种不同的碱敏感性也很明显，这表明非对映体对之间的化学差异在DNA中得以保留。这些化学差异可能会影响胸腺嘧啶这种重要的DNA氧化衍生物的生物学特性。
